Lisinopril is a third-generation long-acting angiotensin-converting enzyme (ACE) inhibitor developed by Merck, U.S., clinically used for the treatment of essential hypertension and renal vascular hypertension, having a structural formula as follows:

Lisinopril hydride, with the full name of N2-[1-(S)-ethoxycarbonyl-3-phenylpropyl]-N6-trifluoroacetyl-L-lysine, is an important intermediate for the synthesis of lisinopril, with a structure formula as follows:

There are mainly two methods for preparing lisinopril hydride:
1. It is reported in U.S. Pat. No. 4,925,969 to use ethyl 4-oxo-4-phenylbut-2-enoate as a starting material, and by the addition with trifluoroacetyl lysinate followed by hydrogenation reduction in the presence of palladium on carbon to obtain lisinopril hydride. The synthesis route is as follows:

The major problem in this synthesis route is that the adduct isomer is easily produced during the addition, and an isomer of lisinopril hydride is prepared by the hydrogenation reduction of the adduct isomer; the hydrogenation operation requirement and the catalyst cost are high, and impurities can be easily produced.
2. It is reported in WO2005010028 to use the benzyl protected trifluoroacetyl lysine to react with (R)-ethyl 2-trifluoromethylsulfonyloxy-4-phenylbutyrate, and then subject to catalytic hydrogenation in the presence of palladium on carbon to obtain lisinopril hydride.

The trifluoroacetyl lysine of the synthesis route needs to be protected by ester formation and then deprotected by hydrogenation, which increases the number of preparation steps and costs.
The preparation methods of lisinopril hydride reported in current literatures have the disadvantages of low yields, high costs, and low atomic utilizations of the routes.